Advantages of combined technetium-99m-sestamibi scintigraphy and high-resolution ultrasonography in parathyroid localization: comparative study in 91 patients with primary hyperparathyroidism

OBJECTIVE: To evaluate the usefulness of the combination of Tc-sestamibi/Tc-pertechnetate subtraction scintigraphy (SS) and high-resolution neck ultrasonography (US) in patients with primary hyperparathyroidism (pHPT) undergoing parathyroidectomy. DESIGN AND METHODS: Ninety-one patients with proved pHPT were studied, excluding patients with persistent or recurrent disease. There were 65 (71.4%) women and 26 (28.6%) men, with a median age of 59 years (range 18-78 years). All patients underwent both SS and US prior to surgery, and the results were compared with operative and histological findings. The intraoperative quick-parathyroid hormone assay was available for 52 (57.1%) patients. When multiglandular disease was found, both SS and US were considered truly positive only when at least two enlarged parathyroid (PT) glands had been localized. RESULTS: Eighty-three (91.2%) solitary PT adenomas and three (3.3%) carcinomas were found. Moreover, two (2.2%) patients had a double adenoma and three (3.3%) patients had diffuse PT hyperplasia. The overall sensitivity of combined SS+US was 94.5% (86.8% and 80.4% for SS and US respectively). There was a significant (P<0.05, Student's t-test) difference in size between the PT glands correctly identified and undetected by SS, whereas the site of the removed PT tumors significantly (P<0.05, Fisher exact test) influenced only the US sensitivity. CONCLUSIONS: When the preoperative localization of the PT glands is chosen, the combination of SS and US represents a reliable noninvasive localization technique and should be considered for use in each patient with pHPT undergoing surgery.     

Hyperfunctioning parathyroid tumours in patients with thyroid nodules. Sensitivity and positive predictive value of high-resolution ultrasonography and 99mTc-sestamibi scintigraphy

A series of 112 consecutive patients with primary hyperparathyroidism who underwent both high-resolution neck ultrasonography (US) and 99mTc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) prior to successful parathyroidectomy was reviewed. There were 29 (25.9%) men and 83 (74.1%) women, with a median age of 58 years (range 13-78 years). Patients were divided into two groups, according to the preoperative US findings: group A (87 patients, 77.7%) without thyroid diseases, and group B (25 patients, 22.3%) with either multinodular goitre or a solitary nontoxic thyroid nodule. In group B patients partial or total thyroidectomy was also performed, according to the intraoperative findings and frozen-section examination results. Final histopathology showed 99 (88.4%) solitary parathyroid (PT) adenomas and 3 (2.7%) PT carcinomas, while 10 (8.9%) patients had a multiglandular disease. The sensitivity and positive predictive value (PPV) were (group A vs group B) 79.8% vs 70.8% (P=0.25) and 95.7% vs 94.4% (P=0.58) for US, and 83.3% vs 87.0% (P=0.47) and 95.9% vs 90.9% (P=0.32) for SS respectively. Better but similar (P=not significant) results were obtained in patients with solitary PT tumours: 81.5% vs 77.8% (US) and 85.0 vs 94.1% (SS) sensitivity; 97.1% vs 93.3% (US) and 95.8% vs 88.9% (SS) PPV. Overall, the combination of US and SS was 92.9% sensitive (group A=93.1%, group B=92.0%; P=0.55), and the PPV reached 100% in each group. In conclusion, in patients with primary hyperparathyroidism the results of both US and SS are independent of coexistent thyroid disease, especially in patients with solitary PT tumours.     

The role of colour Doppler ultrasonography in the preoperative localization of parathyroid adenomas

The aim of the present study was to evaluate the diagnostic accuracy and imaging patterns of colour Doppler ultrasonography (US) and compare it with grayscale US, 99m-Tc methoxyisobutylisonitrile (MIBI) scans, and combined US and MIBI scans in the preoperative diagnosis of parathyroid adenomas in patients with primary hyperparathyroidism (pHPT). From June 2007 to June 2011, 36 consecutive patients (seven men and 29 women) with pHPT underwent grayscale US, colour Doppler ultrasonography (CDUS), and 99m-Tc MIBI scans prior to parathyroidectomy with traditional unilateral neck dissection. All 36 patients with pHPT underwent parathyroidectomy at our university hospital. According to histopathology results, the sensitivity, specificity, and accuracy of MIBI and US scan were 88%, 94%, and 91%, and 70%, 100%, and 85%, respectively. The overall sensitivity and specificity of combined US and MIBI was 97% and 100% respectively. The overall sensitivity, specificity, and accuracy of CDUS in the correct diagnosis of parathyroid adenoma were 97%, 100%, and 98.6%, respectively. The sensitivity and specificity of US in the detection of parathyroid adenoma and differentiating it from other cervical masses reached up to 97% and 100%, respectively, by combining CDUS with grayscale evaluations of parathyroid adenoma.     

Localization of parathyroid tumors using endoscopic ultrasonography in primary hyperparathyroidism

Parathyroid adenomas responsible for primary hyperparathyroidism may be difficult to detect preoperatively. Furthermore parathyroid adenomas may arise behind the (nodular) thyroid gland, in a deep cervical location, and plans should be plane. The purpose of the present prospective study was to evaluate echoendoscopy, and to compare its accuracy to that of non invasive tests. Fourteen consecutive patients with primary hyperparathyroidism were prospectively studied. All patients underwent echoendoscopy, ultrasonography (US), CT scanning or magnetic resonance imaging (MRI) and Tc 99m sestamibi scanning before undergoing initial neck exploration. The parathyroid pathology was a solitary adenoma in 13 patients and a 4 glands hyperplasia in one. All tests were corroborating in 5 cases. Four adenomas were localized to the correc tside (33%), and no test accurately localized all hyperplastic glands. EUS, sestamibi and CT scanning or MRI correctly identified 10 parathyroid tumors in 14 cases (71%). US correctly localized only 5 adenomas (sensitivity 36%). The sensitivity of EUS to detect parathyroid adenomas is superior to US (p<0.05) and comparable to that of other non invasive tests. We conclude that EUS may be an useful tool to localize parathyroid lesions. This method may replace US prior to initial neck exploration with further miniaturization of probes, or find an intermediate place among invasive and noninvasive preoperative localization procedures in patients with persistent or recurrent PHPT.     

Noninvasive localization procedures in ectopic hyperfunctioning parathyroid tumors

In primary hyperparathyroidism (pHPT), parathyroidectomy is the treatment of choice, but anatomic variations of ectopic glands may cause surgical failure. Reliable preoperative noninvasive localization procedures would have a positive impact on the operative time and increase recovery rate. We retrospectively evaluated 186 patients with pHPT who were studied before successful parathyroidectomy by double tracer scintigraphy (99mTc-pertechnetate+201TI chloride or 99mTc-pertechnetate +99mTc-sestamibi, 160 patients), ultrasonography (148 patients) and computerized tomography (CT) scan (92 patients). During bilateral neck exploration, 159 (85.5%) single adenomas, 6 (3.2%) parathyroid carcinomas, and 3 (1.6%) double adenomas were found. Moreover, 18 (9.7%) patients had diffuse chief cells parathyroid hyperplasia. Removed parathyroid glands were in ectopic sites in 41 (22.0%) cases, mainly localized in the upper mediastinum or behind the esophagus. The overall sensitivity was 83.5 and 85.2% for 99mTc-pertechnetate+201TI chloride and 99mTc-pertechnetate+99mTc-sestamibi scintigraphy respectively, 80.4% for CT scan and 81.1% for ultrasonography. In patients with ectopic glands, sensitivity was 81.2, 79.5, 73.3 and 81.6% respectively. In 36 out of 41 patients with ectopic glands in whom the removed parathyroids were correctly localized, mean operative time was 95 min, and in 5 patients without preoperative localization it was 260 min. In conclusion, in pHPT, preoperative localization of an enlarged parathyroid is helpful, especially in ectopic adenomas and in anatomic variations in location, and it has been proved to reduce operative time and morbidity rate.     

Preoperative evaluation of parathyroid lesions in patients with concomitant thyroid disease: role of high resolution ultrasonography and dual phase technetium 99m sestamibi scintigraphy

The aim of this study was to evaluate the sensitivity and usefulness of high resolution ultrasonography (US) and dual phase technetium-99m sestamibi (Tc-MIBI) scintigraphy in the preoperative localization of parathyroid lesions in patients with or without thyroid disease and to define the impact of the presence of thyroid disease on these methods. Preoperative US and scintigraphy were performed on 52 patients with primary hyperparathyroidism. Age, gender, preoperative parathyroid hormone level, serum calcium level, serum phosphate level, diameter, location, associated with thyroid abnormality, and results of parathyroid exploration were determined in all patients. The results of US and Tc-MIBI imaging were analyzed and compared with surgical and histopathologic findings. At surgery, 56 parathyroid lesions were found in 52 patients (9 men, 43 women), the parathyroid lesion was solitary (47 adenomas, two hyperplasias), in 2 patients double adenomas were present, in 1 patient three glands was affected by hyperplasia. Twenty-seven patients had concomitant thyroid disease. The overall sensitivity of US and Tc-MIBI scintigraphy was 84% and 73%, respectively. In patients without thyroid disease, the sensitivity of these techniques was 90% and 75%, respectively. In patients with thyroid disease, the sensitivity was 78% and 70%, respectively. In patients with thyroid disease, the combined sensitivity of these techniques was 89%. These results allow the conclusion that, in experienced hands, US is a highly sensitive technique. Especially in patients with no thyroid pathology and typical located gland, US alone should be used as a first step for preoperative localization of parathyroid lesions. When negative, Tc-MIBI scintigraphy is suggested. In patients with concomitant thyroid disease, the combination of US and Tc-MIBI scintigraphy represents a reliable localization technique.     

The role of ultrasound elastography in preoperative localization of parathyroid lesions: a new assisting method to preoperative parathyroid ultrasonography

Background After the definition of minimally invasive procedures, preoperative localization of parathyroid lesions is now crucial. False‐positive results up to 30% were reported by B‐mode grayscale ultrasonography (US) in localization of parathyroid lesions. Parathyroid adenomas are relatively stiff lesions. Ultrasound elastography (USE) can accurately evaluate tissue stiffness and might detect the stiff parathyroid lesions. Objective The aim of this study is to demonstrate whether USE can detect the level of the stiffness and help the preoperative localization of parathyroid lesions during parathyroid ultrasonography examination. Patients The patients who were candidates for parathyroidectomy were prospectively enrolled to this study and were evaluated by USE. Results Seventy‐two patients with 93 parathyroid lesions underwent parathyroidectomy. Sixty‐three patients including three multiple endocrine neoplasia type‐1 patients had primary hyperparathyroidism, three patients with chronic renal disease (CRD) had tertiary hyperparathyroidism, three patients with CRD and two renal transplanted patients had persistent secondary hyperparathyroidism. One patient was excluded. While all parathyroid adenomas exhibited high levels of stiffness (score 3 and 4), 17 (63%) out of 27 parathyroid hyperplasia lesions were shown to have significantly higher elasticity. The evaluation of median strain ratios of parathyroid lesions revealed that parathyroid adenomas demonstrated significantly higher levels of stiffness than hyperplasias (P ≤ 0·001). Conclusions This is the first study that evaluates the ultrasound elastographic features of parathyroid lesions. Parathyroid adenomas were shown to appear as stiff lesions, and half of the hyperplasias showed high elasticity. Parathyroid elastography is a novel technique to evaluate parathyroid lesions and might be a guide for surgeons to determine the type of operation to apply.     

Intraoperative parathyroid hormone assay improves outcomes of minimally invasive parathyroidectomy mainly in patients with a presumed solitary parathyroid adenoma and missing concordance of preoperative imaging

OBJECTIVE: Intraoperative parathyroid hormone assay (IOPTH) is often used during minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism (pHPT). However, several investigators have reported conflicting outcomes, throwing doubt on the real influence of this adjunct on surgical decision-making. The aim of this study was to determine the impact of routine use of IOPTH on the success rate of MIP as the primary outcome, and whether it value-added to surgical decision-making during the operations at our institution. DESIGN: The results of MIP were determined on postoperative follow-up in 177 consecutive patients with pHPT and compared with the results of preoperative imaging, findings at surgery and the value-added accuracy of IOPTH in surgical decisions. PATIENTS: All 177 patients had biochemically documented pHPT and all were referred for first-time surgery. MEASUREMENTS: Group 1 patients (n = 62) underwent a unilateral neck exploration (UNE) without IOPTH, and group 2 patients (n = 115) underwent MIP (either video-assisted or open) with IOPTH. The primary outcome was the cure rate, whereas the secondary outcome was the value-adding of IOPTH to surgical decision-making during MIP. RESULTS: Of the group 1 vs. 2 patients, 57/62 (91.9%) vs. 114/115 (99.1%) were cured (P = 0.01). Five (8.1%) of the group 1 patients were hypercalcaemic postoperatively, owing to an additional, overlooked, hyperfunctioning parathyroid gland, whereas among the 115 group 2 patients, 104 (90.4%) underwent resection of a single parathyroid adenoma, met the Miami criterion, and were cured. The remaining 11 (9.6%) patients did not have an adequate reduction in parathyroid hormone levels and underwent further neck exploration, with resection of additional hyperfunctioning parathyroids in nine of them. One group 2 patient was not cured. However, a decrease of less than 50% of intraoperative parathyroid hormone (iPTH) assay correctly identified the risk of persistent disease in that patient. Another patient in group 2 had a false-negative IOPTH result. The value-added accuracy of IOPTH (correct assay-based surgeon's decision of further neck exploration) was demonstrated in 3 of 78 group 2 patients with concordant results of both imaging studies vs. 7 of 37 group 2 patients with only one positive imaging study, or 3.8 vs. 18.9% of patients (P = 0.007). CONCLUSIONS: Routine use of IOPTH significantly improves cure rates of MIP in comparison to open image-guided UNE without IOPTH. It is a valuable adjunct in surgical decision-making, allowing for intraoperative recognition and resection of additional hyperfunctioning parathyroid tissue missed by preoperative imaging studies. IOPTH offers substantial value-adding to surgical decision-making, particularly in patients with only one positive imaging study result, and significantly improves the success rate of MIP in these patients. However, in patients with concordant results of two imaging studies, the assay offers significantly lower value-adding to surgical decisions, as a vast majority of patients are cured after removal of a two-image-indexed parathyroid lesion. Despite this, we strongly advocate routine use of IOPTH in all patients undergoing MIP, as this adjunct offers maximum safety for the patient and confidence for the surgeon.     

The effect of calcium and dibutryl-cAMP on the secretion of parathyroid hormone by human parathyroid adenomas in organ culture.

The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3',5'-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.     

Relationship between the dimension of parathyroid glands estimated by ultrasonography and the hyperplastic pattern in patients with renal hyperparathyroidism

In renal hyperparathyroidism (HPT), the parathyroid glands initially proliferate diffusely and polyclonally, and are then transformed to monoclonal nodular hyperplasia with aggressive growth potential. In this study we evaluated the relationship between the maximal dimension of parathyroid glands estimated by ultrasonography (US) and the hyperplastic pattern of parathyroid glands in patients with renal HPT. Between October 1999 and December 2006, 141 patients who underwent total parathyroidectomy (PTx) with forearm autograft in our department were enrolled in this study. In these patients 308 parathyroid glands were detected by US before PTx. The largest dimension of the gland estimated preoperatively by US was correlated closely with its measurement at surgery (R2 was 0.31, P < 0.001). The maximal dimension of diffuse hyperplastic glands was significantly smaller than that of the glands with nodular hyperplastic glands (P < 0.001). There was a strong correlation between the pattern of parathyroid hyperplasia and the glandular diameter when we defined 8 mm as the maximal diameter estimated by US as a cut-off value. As a result of receiver operating characteristic analyses, using these criteria the US technique could predict nodular hyperplasia with a high sensitivity (78.9%) and specificity (78.7%). Parathyroid glands that are enlarged by more than 8 mm in the largest dimension estimated by US may represent glands with nodular hyperplasia.     

Comparison between whole and intact parathyroid hormone assays

The standard measurement of parathyroid hormone (PTH) is the intact PTH (iPTH) assay, which is used for approximately 90% of Japanese dialysis patients. The iPTH assay reacts not only with 1-84?PTH, but also with large truncated fragments of non-1-84?PTH, including 7-84?PTH. On the other hand, the whole PTH assay is specific for 1-84?PTH. The aim of the current study was to define the validity of both whole and intact PTH assays. A total of 738 hemodialysis patients were enrolled from twelve dialysis services. The serum PTH level was evaluated by both intact and whole PTH assays simultaneously. Non-1-84?PTH was determined by subtracting the whole PTH value from that of the intact PTH assay. The median level of whole PTH was 121?pg/mL, and that of iPTH was 210?pg/mL. The whole PTH assay had a very high correlation with the iPTH assay (r?=?0.870, P?相似文献   

Reduced p18INK4c, p21CIP1/WAF1 and p27KIP1 mRNA levels in tumours of primary and secondary hyperparathyroidism

OBJECTIVE: Hyperparathyroidism (HPT) refers to states of excessive production of parathyroid hormone (PTH). The eukaryotic cell cycle is driven forward by cyclins and their cyclin-dependent kinase (CDK) partners. Cyclin-dependent kinase inhibitors (CKIs), which generally inhibit cell cycle progression, modulate the activity of cyclin-CDK complexes. DESIGN: In order to quantify the expression of the CKI genes p18, p21, and p27 semiquantitative RT-PCR with mRNA specific-primers was performed on four normal parathyroid biopsies, 31 parathyroid adenomas of primary HPT and 13 hyperplastic glands from uraemic patients with secondary HPT. PATIENTS: Parathyroid adenomas and secondary hyperplastic glands were obtained from 31 and 13 randomly selected patients undergoing parathyroidectomy in the clinical routine, respectively. Four normal parathyroid gland biopsies were obtained at surgery for pHPT or from normocalcemic patients undergoing thyroidectomy for goitre. RESULTS: The relative p27 expression (p27/GAPDH) was significantly reduced in parathyroid adenomas compared to normal parathyroid gland biopsies. Furthermore, 42% and 53% of the parathyroid adenomas displayed undetectable p18 and p21 expression levels, respectively. All 13 adenomas that lacked p18 expression showed undetectable p21 expression. The p18 expression was significantly lower in tumours of uraemic sHPT as compared to normal parathyroids and an undetectable expression level was observed for p21 and p27 in 61% and 53%, respectively. CONCLUSION: Parathyroid adenomas and secondary hyperplastic glands exhibit aberrant reduced expression of the CKIs p18, p21, and p27. This suggests that deranged collaboration of different CKIs may contribute to the development of both primary and secondary HPT.     

Large carboxy-terminal parathyroid hormone (PTH) fragment with a relatively longer half-life than 1-84 PTH is secreted directly from the parathyroid gland in humans

OBJECTIVE: It was discovered that an immunoreactive large carboxy-terminal parathyroid hormone (PTH) fragment (large C-PTH), likely 7-84 PTH, is present in the circulation. However, very little is known about the production and metabolism of this large C-PTH. Combining a whole molecule PTH (whole PTH) immunoradiometric assay (IRMA) specifically for 1-84 PTH and an intact PTH (iPTH) IRMA for the sum of 1-84 PTH and large C-PTH, we were able to assess the circulating level of this large C-PTH as well as the glandular secretion and metabolism of this large C-PTH in primary hyperparathyroidism (pHPT). METHODS: This study consisted of two patient groups consisting of 77 pHPT patients with a single adenoma. Of these, 43 comprised the venous sampling study group and 70 comprised the intra-operative PTH study group. (Seven patients belonged only to the former group, 34 patients to only the latter group, and 36 patients to both groups.) Preoperatively, blood samples were drawn from the bilateral internal jugular vein by ultrasonographic guidance and from the peripheral vein (n=43). During surgery, blood samples were drawn after anesthesia (basal level), before excision (pre-excision level) of one enlarged parathyroid gland, and at 5, 10, and 15 min post-excision (n=70). RESULTS: There were 26 patients whose iPTH assay levels differed by more than 10% between the right and left internal jugular. In 24 of the 26 patients, the large C-PTH levels obtained from the adenoma side were significantly higher than those from the contralateral side (117+/-135 vs 43+/-33 pg/ml, P<0.001). The plasma whole PTH values decreased more rapidly than the iPTH values after parathyroidectomy (P<0.001). CONCLUSIONS: Our study has demonstrated that the large C-PTH, likely 7-84 PTH, is directly released from the parathyroid gland in humans. Since the half-life of 1-84 PTH is much shorter than large C-PTH, likely 7-84 PTH, it would be advantageous to use an assay that specifically measures 1-84 PTH for intra-operative monitoring of parathyroidectomy.     

Molecular pathology of parathyroid tumors.

Primary hyperparathyroidism (pHPT), generally caused by a monoclonal parathyroid adenoma, is a common endocrinopathy. Until recently, the genesis of the disease was poorly understood but during the past decade the molecular pathology of parathyroid tumor development has begun to be unveiled. This review summarizes recent advances in our understanding of genetic predisposition to pHPT, and the role of vitamin D receptor gene (VDR) variants in development of the disease. It has been shown that the multiple endocrine neoplasia tumor suppressor gene (MEN1) is mutated in parathyroid adenomas, and overexpression of the cyclin D1 oncogene [PRAD1 (parathyroid adenoma 1)] seems to contribute to parathyroid tumorigenesis. Several familial hyperparathyroid disorders have been studied, and the identification and characterization of the disease-causing genes have contributed to our understanding of parathyroid physiology and pathophysiology.     

Parathyroid incidentaloma discovered during thyroid ultrasound imaging

We report two patients with incidentally discovered enlarged parathyroid glands while performing neck ultrasonography (US) for thyroid nodules. The parathyroid masses were seen as hypoechoic, homogeneous, oval nodules, separated from the thyroid gland. Both patients were completely asymptomatic, although subclinical evidence of hyperparathyroidism (serum PTH and calcium levels in the upper limit of the normal range, increased ionized serum calcium, osteocalcin, urinary calcium and hydroxyproline) was subsequently found in one patient. An enhanced uptake on sesta-MIBI scinti scan was concordant with the US finding in the two cases. PTH levels in the wash-out from the US-guided fine needle aspiration biopsy, confirmed the parathyroid origin of the lesions. Cytology and immunocytochemistry were, in our cases, unreliable diagnostic procedures. The extensive use of US imaging in thyroid pathology may increase the finding of US incidentally discovered parathyroid adenomas. The early detection of silent parathyroid pathologic findings may extend the natural history of these masses to a preclinical stage. Further investigations are necessary to evaluate the evolution of parathyroid incidentalomas and therefore their clinical significance.     

Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism

To investigate the SDHAF2 gene and its effect on primary hyperparathyroidism. Parathyroid tumors causing primary hyperparathyroidism (pHPT) are one of the more common endocrine neoplasias. Loss of heterozygosity at chromosome 11q13 is the most common chromosomal aberration in parathyroid tumors occurring in about 40% of sporadic tumors. Only 15-19% display somatic mutations in the MEN1 gene, which suggest that this chromosomal region may harbor additional genes of importance in parathyroid tumor development. The SDHAF2 (formerly SDH5) gene is a recently identified neuroendocrine tumor suppressor gene at this locus, and inherited mutations of the SDHAF2 gene has been linked to familial paraganglioma. We demonstrate that the SDHAF2 gene is expressed in parathyroid tissue using RT-PCR. Because detection of inactivating mutations is the major criterion for validating a candidate tumor suppressor, we used automated sequencing of the coding region and intron/exon boundaries in 80 sporadic parathyroid adenomas from patients with pHPT. A known polymorphisms (A to G substitution; rs879647) was identified in 9/80 parathyroid tumors but no tumor-specific somatic mutational aberrations, such as nonsense, frameshift, or other inactivating mutations were identified. The SDHAF2 gene is expressed in parathyroid tissue. However, somatic mutations of the SDHAF2 tumor suppressor gene are unlikely to frequently contribute to parathyroid tumor development in sporadic pHPT.     

Mediastinal ectopic parathyroid adenoma: report of two cases successfully treated by VATS approach

Ectopic parathyroid adenomas are the cause of approximately one in four cases of primary hyperparathyroidism (pHPT). Most ectopic parathyroid adenomas are located adjacent to the upper thymus gland and can be resected with a collar incision. In rare cases, however, adenomas located in the chest require a transsternalor transthoracic approach. Due to the high rate of morbidity with a sternotomy or thoracotomy, minimally invasive methods such as video-assisted thoracoscopic surgery (VATS) or video-assisted mediastinoscopic surgery (VAMS) are becoming increasingly popular.We present two cases with primary hyperparathyroidism due to mediastinal ectopic parathyroid adenoma that were successfully treated by VATS approach.     

Absence of response to human parathyroid hormone in athymic mice grafted with human parathyroid adenoma, hyperplasia or parathyroid cells maintained in culture

In athymic mice we have developed a model of long-term human PTH hypersecretion, using xenotransplantation of respectively parathyroid gland fragments obtained from patients with primary (primary) or secondary (secondary) uremic hyperparathyroidism (HPT), and parathyroid cells maintained in culture from patients with secondary uremic HPT. Both grafted parathyroid tissue fragments and cultured cells induced prolonged and marked secretion of human intact PTH (iPTH) in nude mice. Despite extremely high plasma iPTH levels, hypercalcemia or hypophosphatemia was not observed. Moreover, PTH secretion was not significantly modified by low-calcium, high-phosphate diet for 3 weeks. Four mice which had a mean plasma human iPTH level of 237+/-152 pg/ml for more than 9 months and 4 age-matched, sham-grafted control mice with undetectable human iPTH levels underwent bone histomorphometry examination. No difference was found between the two groups with respect to active bone resorption surface or number of osteoclasts/mm2. We hypothesize that the characteristic deficit of T cell function and of cytokine and growth factor production may protect nude mice with chronic hypersecretion of human PTH from hypercalcemia and bone lesions. We suggest that this strain of mice could be used for better understanding the relationship between cytokines and bone turnover.     

Sensitivity and specificity of the fine needle aspiration biopsy of the thyroid: clinical point of view

INTRODUCTION: The rates of sensitivity and specificity of fine needle aspiration biopsy (FNAB) for the diagnosis of thyroid malignancy differ considerably among various reported series. These values are influenced by three factors: (a) whether only clearly positive and negative results are considered, or whether the commonly encountered 10-20% of indeterminate/suspicious ones are included; (b) whether adenomas are considered as neoplasms in one group with carcinomas; and (c) whether only histologically proven cases are used in calculations or whether patients with benign clinical follow-up are included. AIM: The aim of the study was to evaluate the sensitivity and specificity of FNABs performed at this institution in the last 7 years from the clinical point of view, considering only benign vs. suspicious/malignant FNAB results (indicating surgery), and benign (including adenomas) vs. malignant definitive histology. STUDY DESIGN: Retrospective study comparing pre-operative FNAB results with definitive histological examination after operation. PATIENTS: A total of 2492 FNABs were performed in 2100 patients (1875 women and 225 men); their ages ranged from 9 to 85 years, with a median of 46 years. Clinical diagnosis was multinodular goitre in 1330, single nodule in 591, Hashimoto's thyroiditis in 147 and subacute thyroiditis in 32 cases. In 148 instances, the nodule was cystic. A history of previous treatment for carcinoma of the thyroid was present in 12 patients. Five hundred and thirty-six patients subsequently underwent thyroid surgery. STATISTICS: The values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were calculated. RESULTS: The sensitivity was 86%, specificity 74%, PPV 34%, NPV 97% and diagnostic accuracy 75%. CONCLUSIONS: The specificity and positive predictive value are low when fine needle aspiration biopsy results are divided into two categories only (these being indication for surgery or not), and when only suspicious/malignant fine needle aspiration biopsies with subsequent malignant histology are considered to be true positive. Nevertheless, the ability to discriminate 11.7% of patients with a 34% probability of malignancy (suspicious/malignant cytology) from 81.2% of patients (benign cytology) with a probability of only 3% is very helpful.